Bracken fern is carcinogenic for many species of animals. Cows and rats are highly susceptible to urinary bladder carcinogenesis by bracken. Milk obtained from cows ingesting bracken fern contains toxic and carcinogenic metabolites not normally present in cow milk. Humans ingesting bracken fern or such milk might be unwittingly exposed to a naturally-occurring plant carcinogen. Toxic and carcinogenic compounds in bracken fern and carcinogenic metabolites in cow milk and in rat urine will be identified and tested for carcinogenic activity utilizing animal and microbiological systems. The possible role of intestinal bacteria in the metabolic activation of the bracken fern will be studied in germ-free rats. Carcinogenic tannin isolated from bracken fern will be tested for carcinogenicity in rodents via different routes of administration. An attempt will be made to inhibit carcinogenicity of this plant by adding phenolic antioxidants, sulfur-containing substances, calcium salts, and nonionic polymers to bracken fern-containing diets fed to rats. The proposed studies are designed to meet the specific study objectives outlined in the Experimental Biology Subflow Phase II-1, 1-A, Phase II-2, 2-A and Phase II-2, 2-B of the National Bladder Cancer Project.